1. Field of the Invention
The present invention relates to methods of identifying drug-resistant bacteria, and particularly to a method of identifying A. baumannii with OXA-131-like drug resistance in diabetic patients.
2. Description of the Related Art
Acinetobacter baumannii is an aerobic gram-negative species of bacteria that is resistant to most antibiotics. Infection by A. baumannii can result in pneumonia and infections of the urinary tract, the bloodstream, and other parts of the body. Left untreated, such infections can result in extended and debilitating convalescence, and may prove fatal. A. baumannii infects those with compromised immune systems, such as the wounded, the elderly, children, those with debilitating diseases, such as diabetes or other diseases or illnesses that might weaken the immune system. A. baumannii has been implicated as the source of nocosomial infections in hospitals and other treatment facilities, with the number of reported nocosomial infections linked to A. baumannii increasing in number in recent years.
The treatment of choice has traditionally been carbapenems (the carbapenems include meropenem, ertapenem, imipenem, doripenem, panapenem, and biapenem), since A. baumannii is resistant to many other antibiotics. The carbapenems are a class of beta-lactam antibiotics effective against a broad spectrum of bacterial infection and resistance to β-lactamases.
In recent years, however, many strains of A. baumannii have shown resistance to the carbapenems. Such resistance results from genes encoding carbapenemases, which have most commonly either been molecular class B metallo-β-lactamases, or molecular class D OXA β-lactamases (so-named for resistance to oxacillin and related compounds). The OXA β-lactamases exhibiting resistance to carbapenems have generally fallen into one of four subgroups: OXA-23-like, OXA-24-like, OXA-58-like, and OXA-51-like. The blaOXA-51-like gene is found in all strains of A. baumannii, and may be used as a marker for identifying A. baumannii. The OXA-51-like subgroup generally exhibits a low level of carbapenem resistance, but when the ISAba1 sequence is upstream of the gene encoding the enzyme, the OXA-51-like enzyme is overexpressed and the gene is more likely to replicate. It is thought that the ISAba1 sequence may act as a promoter when it is upstream from the gene encoding the OXA-51-like enzyme, signaling the start of the gene for messenger RNA to transcribe when expressing the enzyme. As used herein, the term “OXA-51-like” refers to a subgroup of OXA enzymes that includes a group of enzymes with OXA numbers 51, 64, 65, 66, 67, 68, 69, 70, 71, 75, 76, 77, 83, 84, 86, 87, 88, 89, 91, 92, 94 and 95. OXA enzymes may or may not have similar structure, and many of the genes encoding the enzymes may have no more than 20% homology in their sequence. β-lactamases are thought to confer drug resistance to carbapenemases by hydrolysing (or hydrolyzing) and opening the β-lactam ring, rendering the carbapenem ineffectual.
The present inventor has identified four new strains of A. baumannii with novel blaOXA-51-like genes, which encode four enzymes that the inventor refers to as OXA-131-like, the OXA-131 subgroup including OXA-90 (SEQ ID NO: 5), OXA-130 (SEQ ID NO: 6), OXA-131 (SEQ ID NO: 7), and OXA-132 (SEQ ID NO: 8). The OXA-90 gene has the sequence of nucleotides shown in SEQ ID NO: 1 in the attached Sequence Listing. The OXA-130 gene has the sequence of nucleotides shown in SEQ ID NO: 2 in the attached Sequence Listing. The OXA-131 gene has the sequence of nucleotides shown in SEQ ID NO: 3 in the attached Sequence Listing. The OXA-132 gene has the sequence of nucleotides shown in SEQ ID NO: 4 in the attached Sequence Listing.
Each enzyme encodes a β-lactamase that exhibits some degree of carbapenemase activity, and is also resistant to several other antibiotics. Because Infection by A. baumannii may lead to prolonged convalescence or may prove fatal, it is desirable is identify the strain of A. baumannii quickly in order to make an informed selection of an antibiotic for treatment of the infection.
Thus, a method of identifying A. baumannii with OXA-131-like drug resistance in diabetic patients solving the aforementioned problems is desired.